Hospitals across the United States go through some 16,500 liters (35,000 pints) of donated blood for emergency surgeries, scheduled operations, and routine transfusions every single day. Unfortunately, the process is not as simple as just filling someone with blood. It has to be a specific “type” of blood – A, B, AB, or O. If a patient receives the wrong blood type, it could be deadly.
There is a loophole – blood type O, the universal type. Anyone can receive it, making it especially suitable for circumstances when there is an emergency that requires an immediate blood transfusion – a situation with no time to check the person’s blood type. The problem is, there is not enough of this type of blood available. “Around the United States and the rest of the world, there is a constant shortage,” says Mohandas Narla, a red blood cell physiologist at the New York Blood Center in New York City.
Why are there compatibility issues with blood types anyway? Well, the four types are defined by unusual sugar molecules on the surfaces of their red blood cells. Each type has different kinds of sugar coating molecules, called blood antigens. These molecules must be the right type, or else they can cause the immune system to mount a deadly attack on the red blood cells. In other words, if type A molecules enter the bloodstream of type B blood, the type B blood will attack the type A blood cells. Type O cells lack these antigens, making it possible to transfuse that blood type into anyone. That is why it’s the “universal” blood type.
Scientists have tried transforming the second most common blood, type A, by removing its “A-defining” antigens to increase the supply of universal blood. Their attempts were futile as the known enzymes that can strip the red blood cell of the offending sugars aren’t efficient enough to do the job economically. But then, after four years of trying to improve on those enzymes, a team led by Stephen Withers, a chemical biologist at the University of British Columbia (UBC) in Vancouver, Canada, decided to look for a better solution among human gut bacteria. They knew that some of these microbes latch onto the gut wall, where they “eat” the sugar-protein combos called mucins that line it. Mucins’ sugars are similar to the type-defining ones on red blood cells.
“This is a first, and if these data can be replicated, it is certainly a major advance,” says Harvey Klein, a blood transfusion expert at the National Institutes of Health’s Clinical Center in Bethesda, Maryland, who was not involved with the work.
So UBC postdoc Peter Rahfeld collected a human stool sample and isolated its DNA, which in theory would include genes that encode the bacterial enzymes that digest mucins. Then, they chopped this DNA up and loaded different pieces of it into copies of the commonly used lab bacterium Escherichia coli (E. coli). Next, the researchers monitored whether any of the microbes subsequently produced proteins with the ability to remove A-defining sugars. When they tested two of the resulting enzymes at once—adding them to substances that would glow if the sugars were removed—the sugars came right off. The enzymes also worked in human blood.
The enzymes originally come from a gut bacterium called Flavonifractor plautii. Their research revealed that tiny amounts added to a unit of type A blood could get rid of the offending sugars. Withers and his colleagues reported their findings in a paper published in Nature Microbiology. “The findings are very promising in terms of their practical utility,” Narla says. “In the United States, type A blood makes up just under one-third of the supply, meaning the availability of ‘universal’ donor blood could almost double.”
For now, more work is required to ensure that all the offending A antigens have been removed and to make sure the microbial enzymes have not inadvertently altered anything else on the red blood cell that could produce problems. If the process works out, blood specialists suggest it could completely revolutionize blood donation and transfusion. Because type A is more common than type B, the researchers will be focusing on only converting type A. Having the ability to transform type A to type O, Withers says, “would broaden our supply of blood and ease these shortages.”
